Pharmaceutical packaging, such as sealed pockets, blister strips, disks and packs, for doses of medicaments or pharmaceutical compositions in the form of powders, tablets or capsules are well known in the art. As applied in dry powder inhaler technology, the pharmaceutical packaging (e.g., blister strips) generally comprise a base having cavities, pockets or open “blisters” adapted to receive a pharmaceutical composition (e.g., inhalable dry powder), a lid that encloses the opening of each cavity or blister, and an adhesive or bonding layer disposed there between to effect a seal.
It is further well known that pharmaceutical compositions, and in particular, inhaled dry powders, must be maintained in a hermetic environment to maintain a high degree of physical stability in particle size. Only particles having a specific narrow range of aerodynamic diameter size will deposit in the desired location in the pulmonary system. For instance, a particle for local treatment of respiratory conditions such as asthma will have a particle size of 2-5 μm. Particle to particle agglomeration, shifting the particle size outside of this range, will cause the particle(s) to deposit away from the target region of the lung. Such agglomeration has been associated with moisture ingress into the pharmaceutical packaging (i.e., blister). Particle sizes, either in aerodynamic or geometric measures, referred to herein relate to a particles effective particle size. Effective particle size denotes the apparent particle size of a body without distinction as to the number of individual particles which go to make up that body, i.e., no distinction is made between the single particle of given size and an agglomerate of the same size which is composed of finer individual particles.
Similarly, exposure of a pharmaceutical composition to high temperatures can, and in many instances will, undermine the stability and, hence, efficacy of the pharmaceutical composition. Accordingly, it is important to closely monitor the environmental conditions to which a pharmaceutical composition is exposed to ensure that the pharmaceutical composition's physical and chemical stability has not been degraded.
Various prior art sensors have been employed to monitor environmental conditions proximate a pharmaceutical composition. However, as discussed below, most of the noted sensors are not suitable for use “inside” pharmaceutical packaging, and in particular, blister packs.
For example, surface acoustic wave devices, such as the humidity sensors disclosed by U.S. Pat. No. 5,739,416, require a direct physical connection to the sensor. Since blister packs containing pharmaceutical compositions are sealed, any direct connection to a sensor in an individual blister is impractical. On the other hand, sensors not disposed within the packaging do not necessarily provide an accurate indication of conditions within the interior, particularly with respect to humidity. Further, surface acoustic wave sensors are relatively expensive and, hence, not cost effective for use in commercial applications.
Similar problems exist with conventional temperature sensors. Relatively simple systems employing conventional thermostats as well as more complex systems, such as those disclosed in U.S. Pat. No. 4,357,114 that rely on changing magnetic flux, still require a direct electrical connection to the sensor. As such, these technologies are generally unsuitable for use within sealed pharmaceutical packaging.
Fiber optic and laser telemetry sensors have also been employed to monitor environmental conditions. Illustrative is the fiber optic based moisture sensor disclosed in U.S. Pat. No. 5,319,975. However, this technology requires precise orientation of the sensor as well as a visual connection.
Another method of remote determination of one or more environmental conditions is to monitor the induced resonant vibration of a magneto elastic strip or sensor. A basic example of this technology is in the field of electronic article surveillance where magneto acoustic tags are excited by a magnetic field and the corresponding mechanical resonance is then detected (see, e.g., U.S. Pat. No. 5,565,847).
An extrapolation of this technology is to monitor the acoustic or electromagnetic signal produced by a resonating magneto elastic sensor to determine an environmental condition. For example, it is well known that the resonant frequency of a magneto elastic material varies with temperature. It is also well known that applying a mass changing, moisture sensitive coating to a magneto elastic material causes the resonant frequency to vary with relative humidity. Various conventional sensor systems are based in significant part on these noted principles.
By utilizing selective coatings that vary according to a desired condition or conditions, other environmental conditions can also be determined. Illustrative are the pH sensors disclosed in C. A. Grimes, A Remotely Interrogatable Magnetochemical pH Sensor, IEEE Transactions on Magnetics 33:5(1997), pp. 3412-3414.
A significant challenge still, however, exists in incorporating a suitable sensor into the often limited space provided by existing pharmaceutical packaging. Indeed, most pharmaceutical packaging, such as an individual blister in a blister pack, have extremely limited internal space.
For example, in Jain, et al., Magnetoacoustic Remote Query Temperature and Humidity Sensors, Smart Mater. Struck. 9(2000), pp. 502-510 a 12 mm by 24 mm magneto acoustic sensor is disclosed. In U.S. Pat. Nos. 6,359,444, 6,393,921 and 6,397,661, Grimes, et al. similarly disclose magneto acoustic sensors having dimensions that range from 5 mm×37 mm to 10 mm×20 mm.
As is well known in the art, the noted sensors are too large for placement in blister packs and other conventional pharmaceutical packaging. Moreover, such sensors cannot be easily reduced in size, since size reduction substantially changes the resonant and interrogation frequencies, as well as the amplitude of the generated signal. Further, the mass changing, moisture sensitive materials disclosed by Jain et al. would yield unsatisfactory results since they would not exhibit enough mass change when employed in conjunction with a smaller sensor (i.e., magneto elastic strip).
It is therefore an object of the present invention to provide a highly efficient, cost effective means for sensing and/or monitoring environmental conditions and determining values relating thereto within a multitude of pharmaceutical packaging and, in particular, pharmaceutical packaging having limited internal space.
It is another object of the present invention to provide a remote query magneto elastic sensor system and method for sensing and/or monitoring at least one, preferably, a plurality of environmental conditions and determining at least one value relating thereto within pharmaceutical packaging.
It is another object of the present invention to provide a remote sensor system and method for sensing temperature within pharmaceutical packaging.
It is another object of the present invention to provide a remote sensor system and method for sensing the relative or percent humidity within pharmaceutical packaging.